Secreted Protein Acidic and Rich in Cysteine (SPARC), a 37-kDa glycoprotein, participates in the regulation of morphogenesis and cellular differentiation through its modulation of cell-matrix interactions. We have reported previously that SPARC expression significantly impairs medulloblastoma tumor growth in vivo. In this study, we show that the ectopic expression of SPARC induces neuronal differentiation in medulloblastoma cells. Adenovirus-mediated expression of SPARC cDNA (Ad-DsRed-SP) elevated the expression of neuronal markers NeuN, Nestin and MAP-2 in medulloblastoma cells. SPARC expression decreased STAT3 phosphorylation and constitutive expression of STAT3 reversed SPARC-mediated neuronal differentiation. Moreover, our results show that SPARC expression not only inhibited interleukin (IL)-6 but also attenuated IL-6-mediated STAT3 phosphorylation in medulloblastoma cells. Taken together, our results suggest that SPARC induced neuronal differentiation of medulloblastoma tumor cells through its inhibitory effect on IL-6-mediated STAT3 signaling. Immunohistochemical analysis of tumor sections from mice treated with Ad-DsRed-SP showed increased staining for the neuronal markers NeuN, Nestin and MAP-2. Overall, our results demonstrate that SPARC promotes neuronal differentiation and inhibits tumor growth, thereby further supporting the potential use of SPARC as a therapeutic target for medulloblastoma.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2286.

©2010 American Association for Cancer Research
2010